Heme biosynthesis, a complex, multistage, and tightly controlled process, starts with 5-aminolevulinate (ALA) production, which, in metazoa and certain bacteria, is a reaction catalyzed by 5-aminolevulinate synthase (ALAS), a pyridoxal 5'-phosphate (PLP)-dependent enzyme. Functional aberrations in ALAS are associated with several human diseases. ALAS can adopt open and closed conformations, with segmental rearrangements of a C-terminal, 16-amino acid loop and an α-helix regulating accessibility to the ALAS active site...

miRNA biogenesis is a multistage process for generation of a mature miRNA and involves several different proteins. In this work, we have carried out sequence as well as structure based analysis for crucial proteins involved in miRNA biogenesis, namely, Dicer, Drosha, Argonaute (Ago) and Exportin-5 to understand evolution of these proteins in animal kingdom and also to identify key sequence and structural features which are determinants of their function. Our analysis reveals that in animals the miRNA biogenesis pathway first originated in molluscs...

Superhelices, which are induced by the twisting and coiling of double-helical DNA in chromosomes, are thought to affect transcription, replication, and other DNA metabolic processes. In this study, we report the effects of negative supercoiling on the unwinding activity of simian virus 40 large tumor antigen (SV40 TAg) at a single-molecular level. The supercoiling density of linear DNA templates was controlled using magnetic tweezers and monitored using a fluorescent microscope in a flow cell. SV40 TAg-mediated DNA unwinding under relaxed and negative supercoil states was analyzed by the direct observation of both single- and double-stranded regions of single DNA molecules...

Interactions between protein domains and their position and movement relative to each other are essential for the stability and normal functioning of a protein molecule. Features of the movement of domains may define the mechanism of enzymatic reactions. Therefore, the description of this motion is an important task in the analysis of the structures and functions of multidomain proteins. In the current work, we investigated the influence of pressure and temperature on changes in the movement of the two domains of the protein Nip7, expressed by deep-water (P...

Over 100 variants have been designed and studied, using multiple docking methods such as Autodock Vina, ArgusLab, Molegro Virtual Docker (MVD), and Hex-Cuda, to study the effect of alteration in the structure of carbamate based acetylcholyne esterase (AChE) inhibitors. 16 selected systems were then subjected to 14 ns molecular dynamics (MD) simulations. Results from all the docking methods are in agreement. Variants that involved biphenyl substituents possess the most negative binding energies in the -37.64 to -39...

Isoprenaline hydrochloride is a potential cardiovascular drug helps in the smooth functioning of the heart muscles. So, we have performed the binding study of ISO with BSA. This study was investigated by UV absorption, fluorescence, synchronous fluorescence, circular dichroism etc. The analysis of intrinsic fluorescence data showed the low binding affinity of ISO. The binding constant Kb was 2.8×103 M-1 and binding stoichiometry (n) was approximately one and the Gibb's free energy change at 310 K was determined to be -8...

Chikungunya virus nsP2 replication protein is a cysteine protease, which cleaves the nonstructural nsP1234 polyprotein into functional replication components. The cleavage and processing of nsP1234 by nsP2 protease is essential for the replication and proliferation of the virus. Thus, ChikV nsP2 protease is a promising target for antiviral drug discovery. In this study, the crystal structure of the C-terminal domain of ChikV nsP2 protease (PDB ID: 4ZTB) was used for structure based identification and rational designing of peptidomimetic inhibitors against nsP2 protease...

It was reported that bovine α-lactalbumin (BLA) as an important whey protein can be utilized as valuable vehicle for metal ions. The goal of this study was to investigate the interaction of BLA with bisdemethoxycurcumin (BDMC), Diacetylcurcumin (DAC), and diacetylbisdemethoxycurcumin (DABC) as three bioactive compounds by fluorescence quenching measurements and docking studies. It was observed that these ligands come closer to tryptophan residues and quench their emission without any change in their micro region polarity...

6-Hydroxymethyl-7,8-dihydropterin pyrophosphokinase (HPPK) is a promising antimicrobial target involved in the folate biosynthesis pathway. Although, the results from crystallographic studies of HPPK have attracted a great interest in the design of novel HPPK inhibitors, the mechanism of action of HPPK due to inhibitor binding remains questionable. Recently, mercaptoguanine derivatives were reported to inhibit the pyrophosphoryl transfer mechanism of Staphylococcus aureus HPPK (SaHPPK). The present study is an attempt to understand the SaHPPK-inhibitors binding mechanism and to highlight the key residues that possibly involve in the complex formation...

Bis(indolyl)methane (BIM) as one of the main active components of anticancer and antibacterial drugs is applied in medicinal and extensive area of chemistry. In this research interaction of human and bovine serum albumins, as drug carriers with BIM was investigated using spectroscopy methods and molecular modeling study. The fluorescence quenching measurements at the rage of 293 to 310 K revealed that the quenching mechanisms for human and bovine serum albumins are static and dynamic processes, respectively...

The present study was carried out to characterize ACE inhibitory peptides which are release from the trypsin hydrolysate of wheat gluten protein. The binding of two inhibitory peptide (P4 and P6) to human serum albumin (HSA) under physiological conditions has been investigated by multi- spectroscopic in combination with molecular modeling techniques. Time-resolved and quenching fluorescence spectroscopies results revealed that the quenching of HSA fluorescence by P4 and P6 in the binary and ternary systems caused HSA-peptides complexes formation...

Acetylcholinesterase (AChE) is an important enzyme responsible for Alzheimer disease (AD), as per report, keto-enol form of curcumin inhibits this enzyme. The present study aims to understand the binding mechanism of keto-enol curcumin with the recombinant human Acetylcholinesterase (rhAChE) from its conformational flexibility, intermolecular interactions, charge density distribution and the electrostatic properties at the active site of rhAChE. To accomplish this, a molecular docking analysis of curcumin with the rhAChE was performed, which gives the structure and conformation of curcumin in the active site of rhAChE...

Structure-based screening approach targeting mGlu2 receptor was carried out to identify good chemical starting points for anti-epileptic therapy. Interactive modes of final 12 compounds identified on the basis of screening of Asinex library, binding energy analysis, ADME profiling with special emphasis for CNS ranges, and toxicity analysis were studied and showed good binding modes in the mGluR2-active site. Enrichment studies for validating screening protocol were carried out which gave ROC values 0.98 (AUC = 0...

The histone-like (HU) protein is one of the major nucleoid-associated proteins involved in DNA supercoiling and compaction into bacterial nucleoid as well as in all DNA-dependent transactions. This small positively charged dimeric protein binds DNA in a non-sequence specific manner promoting DNA super-structures. The majority of HU proteins are highly conserved among bacteria; however, HU protein from Mycoplasma gallisepticum (HUMgal) has multiple amino acid substitutions in the most conserved regions, which are believed to contribute to its specificity to DNA targets unusual for canonical HU proteins...

Antifreeze proteins (AFPs), found in certain vertebrates, plants, fungi and bacteria have the ability to permit their survival in subzero environments by thermal hysteresis mechanism. However, the exact mechanism of ice growth inhibition is still not clearly understood. Here four long explicit molecular dynamics (MD) simulations have been carried out at two different temperatures (277K and 298 K)with and without glycan to study the conformational rigidity of the Ocean pout type III antifreeze protein in aqueous medium and the structural arrangements of water molecules hydrating its ice binding surface...